<i>CYP2D6</i> polymorphism rs1065852 significantly increases the risk of type 2 diabetes

Genetic variations within the cytochrome P450 (CYP) gene family are significant determinants of type 2 diabetes mellitus (T2DM) susceptibility. This study aimed to investigate the association between <i>CYP2C8</i> and <i>CYP2D6</i> gene variants and the risk of T2DM. We conducted a case-control study involving 512 individuals with T2DM and 515 controls. Genotyping of <i>CYP2C8</i> and <i>CYP2D6</i> polymorphisms was performed using the Agena MassARRAY system. Logistic regression analysis was employed to estimate the odds ratios (ORs) and 95% confidence intervals (CIs), thereby assessing the relationship between these genetic variants and T2DM risk. Additionally, multifactor dimensionality reduction (MDR) was utilized to assess the potential interaction effects of SNPs on T2DM risk. The study found a strong correlation between rs1065852 and increased risk of T2DM in overall (A vs. G: OR = 1.22, 95% CI: 1.03–1.45, <i>p</i> = .024; AA vs. GG: OR = 1.46, 95% CI: 1.04–2.06, <i>p</i> = .031; AA–AG vs. GG: OR = 1.36, 95% CI: 1.04–1.79, <i>p</i> = .026; additive: OR = 1.21, 95% CI: 1.02–1.44, <i>p</i> = .027), males and age &lt; 59 subgroups. However, there is no significant association between the <i>CYP2C8</i> polymorphisms (rs1934953, rs1934951, rs2275620 and rs17110453) and T2DM risk. MDR analysis results showed that the best model was the one locus model (rs1065852, testing accuracy = 0.534; OR = 1.39; 95% CI: 1.05–1.85; <i>p</i> = .023; CVC = 10/10), indicating that rs1065852 is an independent risk factor for T2DM. This study suggests that rs1065852 (<i>CYP2D6</i>) is an independent risk factor for T2DM. Further research is warranted to validate these results and explore their clinical implications.